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Ahmed Saad aly

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Papers by Ahmed Saad aly

The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation

Scientific reports, Jan 27, 2017

The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for ... more The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for survival of Plasmodium falciparum within human erythrocytes. Accordingly, a PA analog α-PanAm showed potent activity against blood stage parasites in vitro; however, its efficacy in vivo and its mode of action remain unknown. We developed a new synthesis route for α-PanAm and showed that the compound is highly effective against blood stages of drug-sensitive and -resistant P. falciparum strains, inhibits development of P. berghei in hepatocytes, and at doses up to 100 mg/kg also inhibits blood stage development of P. chabaudi in mice. We used yeast and its pantothenate kinase Cab1 as models to characterize mode of action of α-PanAm and found that α-PanAm inhibits yeast growth in a PA-dependent manner, and its potency increases dramatically in a yeast mutant with defective pantothenate kinase activity. Biochemical analyses using (14)C-PA as a substrate demonstrated that α-PanAm is a compe...

Measurements of prostaglandin biosynthesis in the gastrointestinal tract: Biochemical and technical problems

Prostaglandins, 1981

The special features of prostaglandin biochemistry, of importance for investigation of the possib... more The special features of prostaglandin biochemistry, of importance for investigation of the possible physiological roles of prostaglandins, are briefly reviewed. The formation of prostaglandins and related compounds from endogenous and exogenous arachidonic acid in homogenates of human gastric mucosal and muscle-serosal layers is described. These preliminary data seem to indicate that a low conversion of exogenous precursor does not necessarily mean that the capacity of the tissue to synthesize prostaglandins from endogenous precursor is low.

Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

mBio, Aug 29, 2017

In sexually reproducing organisms, meiosis is an essential step responsible for generation of hap... more In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C2H2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (P < 0.0001) than mice infected with wild-type (WT) parasites. In mosquito transmission experiments, the infectivity of KO and Trunc parasites was severely compromised (>95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patte...

Genetic Characterization of Coenzyme A Biosynthesis Reveals Essential Distinctive Functions during Malaria Parasite Development in Blood and Mosquito

Frontiers in cellular and infection microbiology, 2017

Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In ... more Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate). Recently, putative pantothenate transporter (PAT) and pantothenate kinases (PanKs) were functionally characterized in P. yoelii. PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages. All enzymes of this pathway were targeted for deletion or deletion/complementation analyses by knockout/knock-in plasmid constructs to reveal their essential roles in P. yoelii life cycle stages. The intermediate enzymes PPCS (Phosphopantothenylcysteine Synthase), PPCDC (Phosphopantothenylcysteine Decarboxylase) were shown to be dispensable for asexual...

Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

Scientific reports, Sep 20, 2016

The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid ... more The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and...

APlasmodiumα/β-hydrolase modulates the development of invasive stages

Cellular Microbiology, 2015

The bud emergence (BEM)46 proteins are evolutionarily conserved members of the α /β-hydrolase sup... more The bud emergence (BEM)46 proteins are evolutionarily conserved members of the α /β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a Plasmodium BEM46-like protein (PBLP) and characterized it throughout the life cycle of the rodent malaria parasite Plasmodium yoelii. The Plasmodium BEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P. yoelii knockout (Δpblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δpblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type (WT) parasites. Δpblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although Δpblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with Δpblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation. These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle.

Live genetically attenuated malaria vaccine

Method for inoculating a vertebrate host against malaria, by administering to the host a live Pla... more

JISC: Adaptive Stream Processing Using Just-In-Time State Completion

The continuous and dynamic nature of data streams may lead a query execution plan (QEP) of a long... more The continuous and dynamic nature of data streams may lead a query execution plan (QEP) of a long-running continuous query to become suboptimal during execution, and hence will need to be altered. The ability to perform an efficient and flawless transition to an equivalent, yet optimal QEP is essential for a data stream query processor. Such transition is challenging for plans with stateful binary operators, such as joins, where the states of the QEP have to be maintained during query transition without compromising the correctness of the query output. This paper presents Just-In-Time State Completion (JISC); a new technique for query plan migration. JISC does not cause any halt to the query execution, and thus allows the query to maintain steady output. JISC is applicable to pipelined as well as eddy-based query evaluation frameworks. Probabilistic analysis of the cost and experimental studies show that JISC increases the execution throughput during the plan migration stage by up to an order of magnitude compared to existing solutions.

Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

Results in Pharma Sciences, 2012

Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with ... more Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacinloaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, twocomponent bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye.

Indexing recent trajectories of moving objects

Proceedings of the 22nd ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems, 2014

The plethora of lacation-aware devices has led to countless locationbased services in which huge ... more The plethora of lacation-aware devices has led to countless locationbased services in which huge amounts of spatio-temporal data get created everyday. Several applications requie efficient processing of queries on the locations of moving objects over time, i.e., the moving object trajectories. This calls for efficient trajectory-based indexing methods that capture both the spatial and temporal dimensions of the data in a way that minimizes the number of disk I/Os required for both updating and querying. Motivated by applications that require only the recent history of a moving object's trajectory, this paper introduces the trails-tree; a disk-based data structure for indexing recent trajectories. The trails-tree maintains a temporalsliding window over the trajectories and uses: (1) an in-memory memo structure that reduces the I/O cost of updates using a lazyupdate mechanism, and (2) a lazy vacuum-cleaning mechanism to delete parts of the trajectories that fall out of the sliding window. Experimental evaluation illustrates that the trails-tree outperforms the state-of-the-art index structures for indexing recent trajectory data by up to a factor of two.

Proceedings of the 2010 ACM SIGMOD International Conference on Management of data, 2010

The identification and processing of similarities in the data play a key role in multiple applica... more The identification and processing of similarities in the data play a key role in multiple application scenarios. Several types of similarity-aware operations have been studied in the literature. However, in most of the previous work, similarity-aware operations are studied in isolation from other regular or similarityaware operations. Furthermore, most of the previous research in the area considers a standalone implementation, i.e., without any integration with a database system. In this demonstration we present SimDB, a similarity-aware database management system. SimDB supports multiple similarity-aware operations as first-class database operators. We describe the architectural changes to implement the similarity-aware operators. In particular, we present the way conventional operators' implementation machinery is extended to support similarity-ware operators. We also show how these operators interact with other similarity-aware and regular operators. In particular, we show the effectiveness of multiple equivalence rules that can be used to extend cost-based query optimization to the case of similarity-ware operations.

M3: Stream Processing on Main-Memory MapReduce

2012 IEEE 28th International Conference on Data Engineering, 2012

The continuous growth of social web applications along with the development of sensor capabilitie... more The continuous growth of social web applications along with the development of sensor capabilities in electronic devices is creating countless opportunities to analyze the enormous amounts of data that is continuously steaming from these applications and devices. To process large scale data on large scale computing clusters, MapReduce has been introduced as a framework for parallel computing. However, most of the current implementations of the MapReduce framework support only the execution of fixed-input jobs. Such restriction makes these implementations inapplicable for most streaming applications, in which queries are continuous in nature, and input data streams are continuously received at high arrival rates. In this demonstration, we showcase M 3 , a prototype implementation of the MapReduce framework in which continuous queries over streams of data can be efficiently answered. M 3 extends Hadoop, the open source implementation of MapReduce, bypassing the Hadoop Distributed File System (HDFS) to support main-memory-only processing. Moreover, M 3 supports continuous execution of the Map and Reduce phases where individual Mappers and Reducers never terminate.

Spatial queries with two kNN predicates

Proceedings of the VLDB Endowment, 2012

The widespread use of location-aware devices has led to countless location-based services in whic... more The widespread use of location-aware devices has led to countless location-based services in which a user query can be arbitrarily complex, i.e., one that embeds multiple spatial selection and join predicates. Amongst these predicates, the k -Nearest-Neighbor ( k NN) predicate stands as one of the most important and widely used predicates. Unlike related research, this paper goes beyond the optimization of queries with single k NN predicates, and shows how queries with two k NN predicates can be optimized. In particular, the paper addresses the optimization of queries with: (i) two k NN-select predicates, (ii) two k NN-join predicates, and (iii) one k NN-join predicate and one k NN-select predicate. For each type of queries, conceptually correct query evaluation plans (QEPs) and new algorithms that optimize the query execution time are presented. Experimental results demonstrate that the proposed algorithms outperform the conceptually correct QEPs by orders of magnitude.

SAP1 is a critical post-transcriptional regulator of infectivity in malaria parasite sporozoite stages

Molecular Microbiology, 2011

Plasmodium salivary gland sporozoites upregulate expression of a unique subset of genes, collecti... more Plasmodium salivary gland sporozoites upregulate expression of a unique subset of genes, collectively called the UIS (upregulated in infectious sporozoites). Many UIS were shown to be essential for early liver stage development, although little is known about their regulation. We previously identified a conserved sporozoite-specific protein, SAP1, which has an essential role in Plasmodium liver infection. Targeted deletion of SAP1 in Plasmodium yoelii caused the depletion of a number of selectively tested UIS transcripts in sporozoites, resulting in a complete early liver stage arrest. Here, we use a global gene expression survey to more comprehensively identify transcripts that are affected by SAP1 deletion. We find an effect upon both the transcript abundance of UIS genes, as well as of select genes previously not grouped as UIS. Importantly, we show that the lack of SAP1 causes the specific degradation of these transcripts. Collectively, our data suggest that SAP1 is involved in a selective posttranscriptional mechanism to regulate the abundance of transcripts critical to the infectivity of sporozoites. Although Pysap1sporozoites are depleted of many of these important transcripts, they confer long-lasting sterile protection against wild-type sporozoite challenge in mice. SAP1 is therefore an appealing candidate locus for attenuation of Plasmodium falciparum.

Maximizing energy utilization of routing in wireless sensor networks

2013 ACS International Conference on Computer Systems and Applications (AICCSA), 2013

ABSTRACT The recent interest in wireless sensor networks has led to a number of routing schemes t... more ABSTRACT The recent interest in wireless sensor networks has led to a number of routing schemes that aim at utilizing the limited resources available at sensor nodes more efficiently. This paper proposes and evaluates &#39;Range Switching&#39;, a routing scheme that aims at increasing the energy utilization of routing protocols. Range switching is applicable to any routing protocol. In this paper, we apply Range Switching to the Gradient Based Routing (GBR) protocol. Experimental results and mathematical analysis show that Range Switching if combined with some network traffic spreading schemes can increase the Wireless Sensor Network (WSN) life-time.

Testbed implementation for Autonomic Network Performance Management of wireless mesh networks

2012 IEEE Globecom Workshops, 2012

ABSTRACT In previous work, we proposed an Autonomic Network Performance Management (ANPM) framewo... more ABSTRACT In previous work, we proposed an Autonomic Network Performance Management (ANPM) framework that follows a control-theoretic approach. We built and verified the framework using network simulations but there were many questions needed to be accurately answered concerning the feasibility of such framework in real networks. In this paper, we are going from simulation to testbed implementation to accurately answer such key questions. We use over-the-counter platforms and open source software to build the test-bed that supports 700 MHz, 2.4 GHz, and 5 GHz frequency bands. Multithreaded code is written to verify the ability of the ANPM framework to react, in a timely manner, to the increase in network traffic load.

Synthesis of Benzofuran Derivatives Using Manganese (III) Acetate Mediated Addition of Β-Dicarbonyl Compounds to Alkyne and Alkenes – a Comparative Study

Synthetic Communications, 2001

In addition; they form new radicals, which cannot be obtained with traditional techniques. Among ... more

Targeted deletion ofSAP1abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection

Molecular Microbiology, 2008

Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS ... more Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS (Upregulated in Infectious Sporozoites) genes. A number of UIS gene products are essential for the establishment of the intrahepatocytic niche. However, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. Herein, we show that a conserved Plasmodium sporozoite lowcomplexity asparagine-rich protein, SAP1 (Sporozoite Asparagine-rich Protein 1), has an essential role in malaria parasite liver infection. Targeted deletion of SAP1 in the rodent malaria parasite Plasmodium yoelii generated mutant parasites that traverse and invade hepatocytes normally but cannot initiate liverstage development in vitro and in vivo. Moreover, immunizations with Pysap1(-) sporozoites confer long-lasting sterile protection against wild-type sporozoite infection. Strikingly, lack of SAP1 abolished expression of essential UIS genes including UIS3, UIS4 and P52 but not the constitutively expressed genes encoding, among others, sporozoite proteins CSP and TRAP. SAP1 localization to the cell interior but not the nucleus of sporozoites suggests its involvement in a post-transcriptional mechanism of gene expression control. These findings demonstrate that SAP1 is essential for liver infection possibly by functioning as a selective regulator controlling the expression of infectivity-associated parasite effector genes.

Design, synthesis, and preliminary evaluation as antimicrobial activity of novel spiro-1, 3-thiazolidine C-acyclic nucleoside analogs

Journal of Sulfur Chemistry, 2008

Synthesis of a new class of 1, 3-thiazolidine nucleoside analogs is described. Reaction of 2-amin... more Synthesis of a new class of 1, 3-thiazolidine nucleoside analogs is described. Reaction of 2-amino-2-deoxy-D-glucopyranose hydrochloride 2 with carbon disulfide yielded 5-hydroxy-4-(D-arabino-1, 2, 3, 4-tetrahydroxybutyl)-thiazolidin-2-thione 3, which on acetylation yielded 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxy-butyl)-thiazolidin-2-thione 4. The acetylated sugar 4 reacted with hydrazonoyl chlorides 1a–f, affording the 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxybutyl)-spiro-13thiazolidine-2,2′ -134thiadiazole derivatives 8a–f. The antibacterial activity of the novel 1, 3-thiazolidine-2,2′ -spiro-134thiadiazole nucleoside analogs is highlighted. All compounds with free NH group in the thiazolidine series 8a–f showed significant biological activity against all the standard strains.

A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocysts

Journal of Experimental Medicine, 2005

The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the... more The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the vertebrate and invertebrate hosts. How malarial parasites exit their host cells after completion of reproduction remains largely unsolved. Inhibitor studies indicated a role of Plasmodium cysteine proteases in merozoite release from host erythrocytes. To validate a vital function of malarial cysteine proteases in active parasite egress, we searched for target genes that can be analyzed functionally by reverse genetics. Herein, we describe a complete arrest of Plasmodium sporozoite egress from Anopheles midgut oocysts by targeted disruption of a stage-specific cysteine protease. Our findings show that sporozoites exit oocysts by parasite-dependent proteolysis rather than by passive oocyst rupture resulting from parasite growth. We provide genetic proof that malarial cysteine proteases are necessary for egress of invasive stages from their intracellular compartment and propose that simila...

The antimalarial activity of the pantothenamide α-PanAm is via inhibition of pantothenate phosphorylation

Scientific reports, Jan 27, 2017

The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for ... more The biosynthesis of the major acyl carrier Coenzyme A from pantothenic acid (PA) is critical for survival of Plasmodium falciparum within human erythrocytes. Accordingly, a PA analog α-PanAm showed potent activity against blood stage parasites in vitro; however, its efficacy in vivo and its mode of action remain unknown. We developed a new synthesis route for α-PanAm and showed that the compound is highly effective against blood stages of drug-sensitive and -resistant P. falciparum strains, inhibits development of P. berghei in hepatocytes, and at doses up to 100 mg/kg also inhibits blood stage development of P. chabaudi in mice. We used yeast and its pantothenate kinase Cab1 as models to characterize mode of action of α-PanAm and found that α-PanAm inhibits yeast growth in a PA-dependent manner, and its potency increases dramatically in a yeast mutant with defective pantothenate kinase activity. Biochemical analyses using (14)C-PA as a substrate demonstrated that α-PanAm is a compe...

Measurements of prostaglandin biosynthesis in the gastrointestinal tract: Biochemical and technical problems

Prostaglandins, 1981

The special features of prostaglandin biochemistry, of importance for investigation of the possib... more The special features of prostaglandin biochemistry, of importance for investigation of the possible physiological roles of prostaglandins, are briefly reviewed. The formation of prostaglandins and related compounds from endogenous and exogenous arachidonic acid in homogenates of human gastric mucosal and muscle-serosal layers is described. These preliminary data seem to indicate that a low conversion of exogenous precursor does not necessarily mean that the capacity of the tissue to synthesize prostaglandins from endogenous precursor is low.

Multifunctional Involvement of a C2H2 Zinc Finger Protein (PbZfp) in Malaria Transmission, Histone Modification, and Susceptibility to DNA Damage Response

mBio, Aug 29, 2017

In sexually reproducing organisms, meiosis is an essential step responsible for generation of hap... more In sexually reproducing organisms, meiosis is an essential step responsible for generation of haploid gametes from diploid somatic cells. The quest for understanding regulatory mechanisms of meiotic recombination in Plasmodium led to identification of a gene encoding a protein that contains 11 copies of C2H2 zinc fingers (ZnF). Reverse genetic approaches were used to create Plasmodium berghei parasites either lacking expression of full-length Plasmodium berghei zinc finger protein (PbZfp) (knockout [KO]) or expressing PbZfp lacking C-terminal zinc finger region (truncated [Trunc]). Mice infected with KO parasites survived two times longer (P < 0.0001) than mice infected with wild-type (WT) parasites. In mosquito transmission experiments, the infectivity of KO and Trunc parasites was severely compromised (>95% oocyst reduction). KO parasites revealed a total lack of trimethylation of histone 3 at several lysine residues (K4, K27, and K36) without any effect on acetylation patte...

Genetic Characterization of Coenzyme A Biosynthesis Reveals Essential Distinctive Functions during Malaria Parasite Development in Blood and Mosquito

Frontiers in cellular and infection microbiology, 2017

Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In ... more Coenzyme A (CoA) is an essential universal cofactor for all prokaryotic and eukaryotic cells. In nearly all non-photosynthetic cells, CoA biosynthesis depends on the uptake and phosphorylation of vitamin B5 (pantothenic acid or pantothenate). Recently, putative pantothenate transporter (PAT) and pantothenate kinases (PanKs) were functionally characterized in P. yoelii. PAT and PanKs were shown to be dispensable for blood stage development, but they were essential for mosquito stages development. Yet, little is known about the cellular functions of the other enzymes of the CoA biosynthesis pathway in malaria parasite life cycle stages. All enzymes of this pathway were targeted for deletion or deletion/complementation analyses by knockout/knock-in plasmid constructs to reveal their essential roles in P. yoelii life cycle stages. The intermediate enzymes PPCS (Phosphopantothenylcysteine Synthase), PPCDC (Phosphopantothenylcysteine Decarboxylase) were shown to be dispensable for asexual...

Genetic Characterization of Plasmodium Putative Pantothenate Kinase Genes Reveals Their Essential Role in Malaria Parasite Transmission to the Mosquito

Scientific reports, Sep 20, 2016

The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid ... more The metabolic machinery for the biosynthesis of Coenzyme A (CoA) from exogenous pantothenic acid (Vitamin B5) has long been considered as an excellent target for the development of selective antimicrobials. Earlier studies in the human malaria parasite Plasmodium falciparum have shown that pantothenate analogs interfere with pantothenate phosphorylation and block asexual blood stage development. Although two eukaryotic-type putative pantothenate kinase genes (PanK1 and PanK2) have been identified in all malaria parasite species, their role in the development of Plasmodium life cycle stages remains unknown. Here we report on the genetic characterization of PanK1 and PanK2 in P. yoelii. We show that P. yoelii parasites lacking either PanK1 or PanK2 undergo normal asexual stages development and sexual stages differentiation, however they are severely deficient in ookinete, oocyst and sporozoite formation inside the mosquito vector. Quantitative transcriptional analyses in wild-type and...

APlasmodiumα/β-hydrolase modulates the development of invasive stages

Cellular Microbiology, 2015

The bud emergence (BEM)46 proteins are evolutionarily conserved members of the α /β-hydrolase sup... more The bud emergence (BEM)46 proteins are evolutionarily conserved members of the α /β-hydrolase superfamily, which includes enzymes with diverse functions and a wide range of substrates. Here, we identified a Plasmodium BEM46-like protein (PBLP) and characterized it throughout the life cycle of the rodent malaria parasite Plasmodium yoelii. The Plasmodium BEM46-like protein is shown to be closely associated with the parasite plasma membrane of asexual erythrocytic stage schizonts and exo-erythrocytic schizonts; however, PBLP localizes to unique intracellular structures in sporozoites. Generation and analysis of P. yoelii knockout (Δpblp) parasite lines showed that PBLP has an important role in erythrocytic stage merozoite development with Δpblp parasites forming fewer merozoites during schizogony, which results in decreased parasitemia when compared with wild-type (WT) parasites. Δpblp parasites showed no defects in gametogenesis or transmission to mosquitoes; however, because they formed fewer oocysts there was a reduction in the number of developed sporozoites in infected mosquitoes when compared with WT. Although Δpblp sporozoites showed no apparent defect in mosquito salivary gland infection, they showed decreased infectivity in hepatocytes in vitro. Similarly, mice infected with Δpblp sporozoites exhibited a delay in the onset of blood-stage patency, which is likely caused by reduced sporozoite infectivity and a discernible delay in exo-erythrocytic merozoite formation. These data are consistent with the model that PBLP has an important role in parasite invasive-stage morphogenesis throughout the parasite life cycle.

Live genetically attenuated malaria vaccine

Method for inoculating a vertebrate host against malaria, by administering to the host a live Pla... more

JISC: Adaptive Stream Processing Using Just-In-Time State Completion

The continuous and dynamic nature of data streams may lead a query execution plan (QEP) of a long... more The continuous and dynamic nature of data streams may lead a query execution plan (QEP) of a long-running continuous query to become suboptimal during execution, and hence will need to be altered. The ability to perform an efficient and flawless transition to an equivalent, yet optimal QEP is essential for a data stream query processor. Such transition is challenging for plans with stateful binary operators, such as joins, where the states of the QEP have to be maintained during query transition without compromising the correctness of the query output. This paper presents Just-In-Time State Completion (JISC); a new technique for query plan migration. JISC does not cause any halt to the query execution, and thus allows the query to maintain steady output. JISC is applicable to pipelined as well as eddy-based query evaluation frameworks. Probabilistic analysis of the cost and experimental studies show that JISC increases the execution throughput during the plan migration stage by up to an order of magnitude compared to existing solutions.

Moxifloxacin in situ gelling microparticles–bioadhesive delivery system

Results in Pharma Sciences, 2012

Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with ... more Antibiotic use for ocular treatments has been largely limited by poor local bioavailability with conventional eyedrops formulations. Here, we developed a controlled delivery system composed of moxifloxacinloaded poly(lactic-co-glycolic acid) (PLGA) microparticles encapsulated in a chondroitin sulfate-based, twocomponent bioadhesive hydrogel. Using a simple and fast electrohydrodynamic spray drying (electrospraying) technique, surfactant-free moxifloxacin-loaded microparticles were fabricated with diameters on the order of 1 μm. A mixed solvent system of methanol/dichloromethane (MeOH/DCM) was employed to prepare the microparticles for the electrospraying processing. Extended release of moxifloxacin using a series of MeOH/DCM mixed solvents was accomplished over 10 days with release concentrations higher than the minimum inhibitory concentration (MIC). In contrast, moxifloxacin loaded directly in hydrogels was released rapidly within 24 h. We observed a decrease of the drug release rate from the microparticles when using an increased percentage of methanol in the mixed solvent from 10% to 30% (v/v), which can be explained by the mixed solvent system providing a driving force to form a gradient of the drug concentrations inside the microparticles. In addition, the delivery system developed in this study, which incorporates a bioadhesive to localize drug release by in situ gelling, may potentially integrate antibiotic prophylaxis and wound healing in the eye.

Indexing recent trajectories of moving objects

Proceedings of the 22nd ACM SIGSPATIAL International Conference on Advances in Geographic Information Systems, 2014

The plethora of lacation-aware devices has led to countless locationbased services in which huge ... more The plethora of lacation-aware devices has led to countless locationbased services in which huge amounts of spatio-temporal data get created everyday. Several applications requie efficient processing of queries on the locations of moving objects over time, i.e., the moving object trajectories. This calls for efficient trajectory-based indexing methods that capture both the spatial and temporal dimensions of the data in a way that minimizes the number of disk I/Os required for both updating and querying. Motivated by applications that require only the recent history of a moving object's trajectory, this paper introduces the trails-tree; a disk-based data structure for indexing recent trajectories. The trails-tree maintains a temporalsliding window over the trajectories and uses: (1) an in-memory memo structure that reduces the I/O cost of updates using a lazyupdate mechanism, and (2) a lazy vacuum-cleaning mechanism to delete parts of the trajectories that fall out of the sliding window. Experimental evaluation illustrates that the trails-tree outperforms the state-of-the-art index structures for indexing recent trajectory data by up to a factor of two.

Proceedings of the 2010 ACM SIGMOD International Conference on Management of data, 2010

The identification and processing of similarities in the data play a key role in multiple applica... more The identification and processing of similarities in the data play a key role in multiple application scenarios. Several types of similarity-aware operations have been studied in the literature. However, in most of the previous work, similarity-aware operations are studied in isolation from other regular or similarityaware operations. Furthermore, most of the previous research in the area considers a standalone implementation, i.e., without any integration with a database system. In this demonstration we present SimDB, a similarity-aware database management system. SimDB supports multiple similarity-aware operations as first-class database operators. We describe the architectural changes to implement the similarity-aware operators. In particular, we present the way conventional operators' implementation machinery is extended to support similarity-ware operators. We also show how these operators interact with other similarity-aware and regular operators. In particular, we show the effectiveness of multiple equivalence rules that can be used to extend cost-based query optimization to the case of similarity-ware operations.

M3: Stream Processing on Main-Memory MapReduce

2012 IEEE 28th International Conference on Data Engineering, 2012

The continuous growth of social web applications along with the development of sensor capabilitie... more The continuous growth of social web applications along with the development of sensor capabilities in electronic devices is creating countless opportunities to analyze the enormous amounts of data that is continuously steaming from these applications and devices. To process large scale data on large scale computing clusters, MapReduce has been introduced as a framework for parallel computing. However, most of the current implementations of the MapReduce framework support only the execution of fixed-input jobs. Such restriction makes these implementations inapplicable for most streaming applications, in which queries are continuous in nature, and input data streams are continuously received at high arrival rates. In this demonstration, we showcase M 3 , a prototype implementation of the MapReduce framework in which continuous queries over streams of data can be efficiently answered. M 3 extends Hadoop, the open source implementation of MapReduce, bypassing the Hadoop Distributed File System (HDFS) to support main-memory-only processing. Moreover, M 3 supports continuous execution of the Map and Reduce phases where individual Mappers and Reducers never terminate.

Spatial queries with two kNN predicates

Proceedings of the VLDB Endowment, 2012

The widespread use of location-aware devices has led to countless location-based services in whic... more The widespread use of location-aware devices has led to countless location-based services in which a user query can be arbitrarily complex, i.e., one that embeds multiple spatial selection and join predicates. Amongst these predicates, the k -Nearest-Neighbor ( k NN) predicate stands as one of the most important and widely used predicates. Unlike related research, this paper goes beyond the optimization of queries with single k NN predicates, and shows how queries with two k NN predicates can be optimized. In particular, the paper addresses the optimization of queries with: (i) two k NN-select predicates, (ii) two k NN-join predicates, and (iii) one k NN-join predicate and one k NN-select predicate. For each type of queries, conceptually correct query evaluation plans (QEPs) and new algorithms that optimize the query execution time are presented. Experimental results demonstrate that the proposed algorithms outperform the conceptually correct QEPs by orders of magnitude.

SAP1 is a critical post-transcriptional regulator of infectivity in malaria parasite sporozoite stages

Molecular Microbiology, 2011

Plasmodium salivary gland sporozoites upregulate expression of a unique subset of genes, collecti... more Plasmodium salivary gland sporozoites upregulate expression of a unique subset of genes, collectively called the UIS (upregulated in infectious sporozoites). Many UIS were shown to be essential for early liver stage development, although little is known about their regulation. We previously identified a conserved sporozoite-specific protein, SAP1, which has an essential role in Plasmodium liver infection. Targeted deletion of SAP1 in Plasmodium yoelii caused the depletion of a number of selectively tested UIS transcripts in sporozoites, resulting in a complete early liver stage arrest. Here, we use a global gene expression survey to more comprehensively identify transcripts that are affected by SAP1 deletion. We find an effect upon both the transcript abundance of UIS genes, as well as of select genes previously not grouped as UIS. Importantly, we show that the lack of SAP1 causes the specific degradation of these transcripts. Collectively, our data suggest that SAP1 is involved in a selective posttranscriptional mechanism to regulate the abundance of transcripts critical to the infectivity of sporozoites. Although Pysap1sporozoites are depleted of many of these important transcripts, they confer long-lasting sterile protection against wild-type sporozoite challenge in mice. SAP1 is therefore an appealing candidate locus for attenuation of Plasmodium falciparum.

Maximizing energy utilization of routing in wireless sensor networks

2013 ACS International Conference on Computer Systems and Applications (AICCSA), 2013

ABSTRACT The recent interest in wireless sensor networks has led to a number of routing schemes t... more ABSTRACT The recent interest in wireless sensor networks has led to a number of routing schemes that aim at utilizing the limited resources available at sensor nodes more efficiently. This paper proposes and evaluates &#39;Range Switching&#39;, a routing scheme that aims at increasing the energy utilization of routing protocols. Range switching is applicable to any routing protocol. In this paper, we apply Range Switching to the Gradient Based Routing (GBR) protocol. Experimental results and mathematical analysis show that Range Switching if combined with some network traffic spreading schemes can increase the Wireless Sensor Network (WSN) life-time.

Testbed implementation for Autonomic Network Performance Management of wireless mesh networks

2012 IEEE Globecom Workshops, 2012

ABSTRACT In previous work, we proposed an Autonomic Network Performance Management (ANPM) framewo... more ABSTRACT In previous work, we proposed an Autonomic Network Performance Management (ANPM) framework that follows a control-theoretic approach. We built and verified the framework using network simulations but there were many questions needed to be accurately answered concerning the feasibility of such framework in real networks. In this paper, we are going from simulation to testbed implementation to accurately answer such key questions. We use over-the-counter platforms and open source software to build the test-bed that supports 700 MHz, 2.4 GHz, and 5 GHz frequency bands. Multithreaded code is written to verify the ability of the ANPM framework to react, in a timely manner, to the increase in network traffic load.

Synthesis of Benzofuran Derivatives Using Manganese (III) Acetate Mediated Addition of Β-Dicarbonyl Compounds to Alkyne and Alkenes – a Comparative Study

Synthetic Communications, 2001

In addition; they form new radicals, which cannot be obtained with traditional techniques. Among ... more

Targeted deletion ofSAP1abolishes the expression of infectivity factors necessary for successful malaria parasite liver infection

Molecular Microbiology, 2008

Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS ... more Malaria parasite sporozoites prepare for transmission to a mammalian host by upregulation of UIS (Upregulated in Infectious Sporozoites) genes. A number of UIS gene products are essential for the establishment of the intrahepatocytic niche. However, the factors that regulate the expression of genes involved in gain of infectivity for the liver are unknown. Herein, we show that a conserved Plasmodium sporozoite lowcomplexity asparagine-rich protein, SAP1 (Sporozoite Asparagine-rich Protein 1), has an essential role in malaria parasite liver infection. Targeted deletion of SAP1 in the rodent malaria parasite Plasmodium yoelii generated mutant parasites that traverse and invade hepatocytes normally but cannot initiate liverstage development in vitro and in vivo. Moreover, immunizations with Pysap1(-) sporozoites confer long-lasting sterile protection against wild-type sporozoite infection. Strikingly, lack of SAP1 abolished expression of essential UIS genes including UIS3, UIS4 and P52 but not the constitutively expressed genes encoding, among others, sporozoite proteins CSP and TRAP. SAP1 localization to the cell interior but not the nucleus of sporozoites suggests its involvement in a post-transcriptional mechanism of gene expression control. These findings demonstrate that SAP1 is essential for liver infection possibly by functioning as a selective regulator controlling the expression of infectivity-associated parasite effector genes.

Design, synthesis, and preliminary evaluation as antimicrobial activity of novel spiro-1, 3-thiazolidine C-acyclic nucleoside analogs

Journal of Sulfur Chemistry, 2008

Synthesis of a new class of 1, 3-thiazolidine nucleoside analogs is described. Reaction of 2-amin... more Synthesis of a new class of 1, 3-thiazolidine nucleoside analogs is described. Reaction of 2-amino-2-deoxy-D-glucopyranose hydrochloride 2 with carbon disulfide yielded 5-hydroxy-4-(D-arabino-1, 2, 3, 4-tetrahydroxybutyl)-thiazolidin-2-thione 3, which on acetylation yielded 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxy-butyl)-thiazolidin-2-thione 4. The acetylated sugar 4 reacted with hydrazonoyl chlorides 1a–f, affording the 5-acetoxy-4-(D-arabino-1, 2, 3, 4-tetraacetoxybutyl)-spiro-13thiazolidine-2,2′ -134thiadiazole derivatives 8a–f. The antibacterial activity of the novel 1, 3-thiazolidine-2,2′ -spiro-134thiadiazole nucleoside analogs is highlighted. All compounds with free NH group in the thiazolidine series 8a–f showed significant biological activity against all the standard strains.

A malarial cysteine protease is necessary for Plasmodium sporozoite egress from oocysts

Journal of Experimental Medicine, 2005

The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the... more The Plasmodium life cycle is a sequence of alternating invasive and replicative stages within the vertebrate and invertebrate hosts. How malarial parasites exit their host cells after completion of reproduction remains largely unsolved. Inhibitor studies indicated a role of Plasmodium cysteine proteases in merozoite release from host erythrocytes. To validate a vital function of malarial cysteine proteases in active parasite egress, we searched for target genes that can be analyzed functionally by reverse genetics. Herein, we describe a complete arrest of Plasmodium sporozoite egress from Anopheles midgut oocysts by targeted disruption of a stage-specific cysteine protease. Our findings show that sporozoites exit oocysts by parasite-dependent proteolysis rather than by passive oocyst rupture resulting from parasite growth. We provide genetic proof that malarial cysteine proteases are necessary for egress of invasive stages from their intracellular compartment and propose that simila...